Epigenetic regulation of miRNA induced by mechanical stress in human chondrocytes

• Project/Area Number: 26462299
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Okayama University
• Principal Investigator: Nishida Keiichiro 岡山大学, 医歯薬学総合研究科, 准教授 (80284058)
• Co-Investigator(Kenkyū-buntansha): 大橋 俊孝 岡山大学, 医歯薬学総合研究科, 教授 (50194262) ; 川畑 智子 岡山大学, 大学病院, 助教 (90600669)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2016: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: miRNA / 軟骨代謝 / メカニカルストレス / マイクロアレイ解析 / エピジェネティクス / HDAC / 疾患修飾性OA治療薬 / 新規疾患修飾性OA治療薬 / microRNA / 軟骨細胞 / ADAM12 / miR-29b

Outline of Final Research Achievements

Human chondro-osteophytes were obtained at the time of total joint arthroplasty from knee joints and hip joints of patients with osteoarthritis (OA). ADAM12, one of the target gene of miRNA29-b was observed in chondrocytes of the proliferative and hypertrophic zones in human chondro-osteophytes by immunohistochemistry. ADAM12 mRNA was up-regulated during chondrogenic differentiation in ATDC5 cells, before up-regulation of type X collagen mRNA. In patients with OA, mechanical forces acting on the sites of soft tissue attachments at the joint margins play a primary role in chondro-osteophyte formation and may cause joint pain leading to impaired activity of daily living. In addition, it has been reported that the haplotypes in the ADAM12 gene are strongly related to the risk of clinical knee OA. Modulation of signaling pathway of miRNA29b-ADAM12 axis may contribute the future development of a novel therapy against OA.

Research Products

• [Journal Article] Dramatic Effect of Tofacitinib on TNFInhibitor Resistant Synovitis: A Case Report. (2016)
  • Author(s): Nishida K, Natsumeda M, Nasu Y, Ezawa K.
  • Journal Title: Rheumatology (Sunnyvale) Volume: 6 Issue: 01 Pages: 185-185
  • DOI: 10.4172/2161-1149.1000185
  • Peer Reviewed / Open Access
• [Journal Article] 関節リウマチ－関節破壊の機序を中心に－ (2015)
  • Author(s): 原田遼三, 西田圭一郎
  • Journal Title: リウマチ科 Volume: 53 Pages: 227-232
• [Journal Article] Hyaluronan suppresses mechanical stress-induced expression of catabolic enzymes by human chondrocytes via inhibition of IL-1β production and subsequent NF-κB activation (2015)
  • Author(s): Ozawa M, Nishida K, Yoshida A, Saito T, Harada R, Machida T, Ozaki T
  • Journal Title: Inflammation Res Volume: 64 Issue: 3-4 Pages: 243-252
  • DOI: 10.1007/s00011-015-0804-2
  • Peer Reviewed
• [Journal Article] 軟骨細胞. リウマチ性疾患における骨軟骨破壊に関わる細胞たち. (2015)
  • Author(s): 西田圭一郎
  • Journal Title: Keynote R.A Volume: 3 Pages: 113-116
• [Presentation] 変形性関節症における骨棘形成へのmiR-29bを介したADAM12の関与 (2017)
  • Author(s): 堀田昌宏, 西田圭一郎, 長谷井 嬢, 古松毅之, 宮澤慎一, 那須義久,中原龍一,竹下歩, 兼田大輔, 櫻井美和, 国定俊之, 尾﨑敏文
  • Organizer: 第30回日本軟骨代謝学会
  • Place of Presentation: 京都市
  • Year and Date: 2017-03-03
• [Presentation] 変形性関節症における骨棘形成に対するADAM12の関与 (2016)
  • Author(s): 堀田昌宏, 西田圭一郎, 古松毅之, 宮澤慎一, 那須義久, 藤原智洋, 中原龍一, 町田崇博, 竹下歩, 兼田大輔, 尾﨑敏文
  • Organizer: 第31回日本整形外科基礎学術集会
  • Place of Presentation: 福岡県博多市
  • Year and Date: 2016-10-13
• [Presentation] メカニカルストレスに対するJAK阻害薬Tofacitinibの軟骨破壊抑制効果 (2015)
  • Author(s): 町田崇博、西田圭一郎、那須義久、中原龍一、堀田昌宏、竹下歩、兼田大輔、尾﨑敏文
  • Organizer: 第26回日本リウマチ学会中国・四国支部学術集会
  • Place of Presentation: 岡山市
  • Year and Date: 2015-12-04
• [Presentation] メカニカルストレスに対するJAK阻害薬Tofacitinibの軟骨破壊抑制効果 (2015)
  • Author(s): 町田崇博、西田圭一郎、那須義久、中原龍一、斎藤太一、堀田昌宏、竹下歩、兼田大輔、尾﨑敏文
  • Organizer: 第30回日本整形外科学会基礎学術集会
  • Place of Presentation: 富山市
  • Year and Date: 2015-10-22
• [Book] 知っておくべき 整形外科医の関節リウマチ診療ABC (2016)
  • Author(s): 西田圭一郎
  • Total Pages: 226
  • Publisher: 文光堂